Researchers at CODA Genomics, LLC, have developed a novel interdisciplinary method, involving both computational and biological methods, to enable the reliable, error free, and economical self-assembly of DMA molecules (synthetic genes). This Phase I application proposes to extend these methods to the simultaneous assembly of multiple genes from thousands of oligonucleotides synthesized on DMA chips. Since the major cost for gene syntheses is the cost of chemically synthesized oligonucleotides, the in situ synthesis of oligonucleotides can greatly reduce this cost. At this price, affordable even to small laboratories, it will be cost advantageous to assemble synthetic genes optimized for expression in hosts of choice rather than to isolate genes from natural sources. The ultimate Phase I goal of this proposal is to simultaneously assemble, and compare, five genes from pools of conventionally synthesized oligonucleotides and the same five genes from pools of oligonucleotides released from a DMA chip. Preliminary data presented in the proposal, demonstrate the feasibility of this Phase I objective. The Phase II goal will be to test the limits of this technology, to drive down the costs of gene synthesis as far as possible, and to bring the self-assembly of synthetic genes to every biomedical research laboratory. These studies will also provide the preliminary information for the design of DNA chips to produce gene libraries of proteins and protein variants for drug discovery studies. [unreadable] [unreadable]